Chinese Herbal Medicines
·
2026
·
IF 11.2
Aifen Liu,Jingyan Hu,Weili Yu,Chuanyu Cang,Chuanjing Shi,Xi Wang,Rui Wang,Xuanwei Cai,Fengbo Zhao,Lei Zhang
Objective Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by ovulatory dysfunction. Formononetin (FMN), a bioactive compound derived from leguminous plants, including Glycyrrhiza uralensis , Trifolium pratense , and Astragalus membranaceus , exhibits anti-inflammatory and anti-fibrotic properties. This study aimed to evaluate the therapeutic effects of FMN in a PCOS rat model and elucidate its underlying molecular mechanisms. Methods A PCOS-like model was established in 3-week-old female Sprague-Dawley rats by daily dehydroepiandrosterone (DHEA) injections. The efficacy of FMN was assessed by monitoring estrous cycles, hormone levels, glucose tolerance, and ovarian tissue morphology. Network pharmacology and transcriptome sequencing were used to predict the molecular targets and signaling pathways of FMN. The binding and stabilizing effects of FMN on suppressor of cytokine signaling 3 (SOCS3) were confirmed using molecular docking, molecular dynamics (MD) simulations, and cellular thermal shift assay (CETSA)-Western blotting (WB) (CETSA-WB). The expression of SOCS3, inflammation- and fibrosis-related markers, and the components of the transforming growth factor beta1 (TGF- β 1)/Smad pathway were quantified by quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry. Functional validation was performed using SOCS3 small interfering RNA (siRNA). Results DHEA successfully induced a PCOS-like phenotype, including disrupted estrous cycle, hyperandrogenism, an elevated luteinizing hormone to follicular stimulating hormone (LH/FSH) ratio, insulin resistance, and abnormal ovarian morphology. FMN treatment significantly reversed these abnormalities and reduced ovarian collagen deposition. Network pharmacology and transcriptome analyses indicated that the therapeutic efficacy of FMN was primarily attributable to its anti-fibrotic and anti-inflammatory properties, with SOCS3 identified as a potential key molecule. Molecular docking and MD simulations, along with CETSA-WB, further revealed that FMN directly binds to SOCS3, enhancing its stability and thereby inhibiting ovarian fibrosis in PCOS. Moreover, qPCR, Western blotting, and immunohistochemistry confirmed that FMN regulates the TGF- β 1/Smad signaling pathway. Importantly, SOCS3siRNA abolished fibrotic-related collagen levels and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) expression, supporting the notion that FMN ameliorates PCOS-induced ovarian fibrosis via SOCS3. Conclusion FMN alleviated ovarian dysfunction and hyperandrogenism in DHEA-induced PCOS rats by stabilizing SOCS3 and inhibiting TGF- β 1/Smad signaling, thereby attenuating ovarian fibrosis and inflammation. This reveals a novel SOCS3-centered mechanism for FMN and underscores its therapeutic potential for PCOS.
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Miao Song,Yilong Cui,Qi Wang,Xuliang Zhang,Jian Zhang,Menglin Liu,Yanfei Li
Aluminum (Al)-induced bone formation and metabolism disorder through inhibition of the TGF-β1/Smad signaling pathway is one of the important mechanisms of bone impairment. Ginsenoside Rg3 (Rg3), a specific biological effector molecule, can provide protection to bones. Previously, we demonstrated that Rg3 can reverse aluminum chloride (AlCl3)-induced oxidative stress and metabolic disorder of bones; however, whether the TGF-β1/Smad signaling pathway is involved in it remains unclear. First, we found that Rg3 attenuated Al-induced bone impairment in vivo and in vitro by relieving structural damage to the femur, increasing MC3T3-E1 cell activity, differentiation, mineralization, inhibition of cell apoptosis, and upregulating the extracellular matrix (ECM) synthesis and the expression of TGF-β1/Smad signaling pathway key factors. Subsequently, in the signal pathway intervention experiment, the protective effect of Rg3 on bone impairment induced by Al was weakened; these results indicate that activating the TGF-β1/Smad signaling pathway is one of the mechanisms of Rg3-attenuated Al-induced bone impairment.
研究领域:
药理学
·
毒理学
·
骨生物学
·
信号转导
✓ 已验证
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2020
·Vol. 22
·期 5
·3687-3694
·
IF 2.1
Yingli Ren,Xiangdong Jian,Zhongchen Zhang,Qiong Ning,Baotian Kan,Li Kong
Paraquat is a highly toxic pesticide, which often causes pulmonary interstitial fibrosis after poisoning, and there is no specific antidote. At present, limited studies have reported that tacrolimus, as an immunosuppressant, can inhibit pulmonary fibrosis, but the specific mechanism remains unknown. The aim of the present study was to demonstrate the effect of tacrolimus on the TGF‑β1 pathway associated with pulmonary fibrosis in paraquat exposed alveolar type II epithelial cells, and to identify the antipulmonary fibrosis mechanism of tacrolimus The rat alveolar epithelial type II RLE‑6TN cell line was exposed to paraquat and treated with or without tacrolimus for 24 h, or with a TGF‑β1 receptor type I/II inhibitor (LY2109761) for 1, 4, 8 or 16 h. MTT assays were used to detect the viability of rat alveolar type II epithelial cells under these different treatment conditions, while the concentrations of TGF‑β1, SMAD3, SMAD7 and connective tissue growth factor (CTGF) in the cell culture supernatant were determined using ELISAs. Additionally, reverse transcription‑quantitative PCR and immunofluorescence were used to analyze the mRNA and protein expression levels of TGF‑β1, SMAD3, CTGF and SMAD7. The results demonstrated that the inhibition of the proliferation of RLE‑6TN cells exposed to 200 nmol/l paraquat was 26.05±2.99%. The inhibition rate of 10 ng/ml tacrolimus on paraquat‑exposed alveolar type II epithelial cells was 18.40±3.49%. The inhibition rate caused by 5 µmol/l LY2109761 was 26.56±4.49%. The expression levels of TGF‑β1, SMAD3 and CTGF, as well as their concentrations in the culture supernatant, were significantly downregulated in the tacrolimus group compared with the paraquat group. However, both the concentration and expression levels of SMAD7 were significantly upregulated in the tacrolimus group compared with the paraquat group. In conclusion, tacrolimus can reduce the levels of TGF‑β1, SMAD3 and CTGF, increase the level of SMAD7 in TGF‑β1 signaling pathway and protect the development of pulmonary fibrosis in paraquat exposed alveolar epithelial cells.
研究领域:
药理学
·
肺病学
·
细胞生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 7
·956-968
·
IF 2.571
Wang Youpeng,Jing Weichao,Qu Wanying,Liu Zhiwei,Zhang Di,Qi Xiaoyu,Liu Lujia
ObjectivesThe aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms.MethodsAllergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin.Key findingsHigh dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-β1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase β (p-IKKβ) and NF-κB.ConclusionsTectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-β1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.
研究领域:
药理学
·
免疫学
·
呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 22
·7669
·
IF 4.6
Hongxing Zheng,Yingjun Hu,Mengli Shao,Simin Chen,Shanshan Qi
Chromium picolinate (CP) is an organic compound that has long been used to treat diabetes. Our previous studies found CP could relieve diabetic nephropathy. Thus, we speculate that it might have a positive effect on diabetic testicular injury. In this study, a diabetic rat model was established, and then the rats were treated with CP for 8 weeks. We found that the levels of blood glucose, food, and water intake were reduced, and body weight was enhanced in diabetic rats after CP supplementation. Meanwhile, in CP treatment groups, the levels of male hormone and sperm parameters were improved, the pathological structure of the testicular tissue was repaired, and testicular fibrosis was inhibited. In addition, CP reduced the levels of serum inflammatory cytokines, and decreased oxidative stress and apoptosis in the testicular tissue. In conclusion, CP could ameliorate testicular damage in diabetic rats, as well as being a potential testicle-protective nutrient in the future to prevent the testicular damage caused by diabetes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Xin Xie,Ting-ting Shen,Hai-lian Bi,Zhuo-lin Su,Zi-qi Liao,Ying Zhang,Lei Shi,Yun-long Xia
Angiotensin II (Ang II) induced Atrial fibrillation (AF) often accompanied with reduced ATRAP which is a negative modulator of Ang II type 1 receptor (AT1R). Melatonin can protect against AF, but the underlying molecular mechanism remains poorly understood. In this study, Ang II was used to induce AF, and AF inducibility and duration were documented telemetrically. Ang II-infused mice had a higher AF incidence, which was associated with atrial fibrosis, inflammation, and oxidative stress. Melatonin partially inhibited these effects, and enforced expression of siRNA-ATRAP in atria counteracted the beneficial role of melatonin. Specifically, melatonin inhibited expression of Ang II-induced proteasome and immunoproteasome subunits β2, β2i, β5, and β5i as well as their corresponding trypsin-like and chymotrypsin-like activities and blocked ATRAP degradation. In turn, this inhibited AT1R-mediated NF-κB signaling, transforming growth factor (TGF)-β1/Smad signaling in the atria, and thereby affected atrial remodeling and AF. Melatonin receptor inhibition by the chemical inhibitor luzindole partially inhibited the inhibitory effects of melatonin on proteasome activity and also Ang II-induced pathological changes in the atria. Overall, our study demonstrates that melatonin protects against Ang II-induced AF by inhibiting proteasome activity and stabilizing ATRAP expression, and these effects are partially dependent on melatonin receptor activation.
研究领域:
心脏病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Peng Wei,Zhang Shiwen,Zhou Wei,Zhao Xinchen,Wang Kexue,Yue Chengxu,Wei Xinyu,Pang Siyan,Dong Wei,Chen Sulian,Chen Changjie,Yang Qingling,Wang Wenrui
A core feature of liver fibrosis is the activation of hepatic stellate cells (HSCs), which are transformed into myofibroblasts and lead to the accumulation of extracellular matrix (ECM) proteins. In this study, we combined in vitro cellular efficacy with in vivo antifibrosis performance to evaluate the outcome of sorafenib (SRF) loaded layered double hydroxide (LDH) nanocomposite (LDH-SRF) on HSCs. The cellular uptake test has revealed that sorafenib encapsulated LDH nanoparticles were efficiently internalized by the HSC-T6 cells, synergistically inducing apoptosis of hepatic stellate cells. Moreover, the apoptosis rate and the migration inhibition rate induced by LDHs-SRF were 2.5 and 1.7 times that of SRF. Western Blot showed that the TGF-β1/Smad/EMT and AKT signaling pathway was significantly inhibited in HSC-T6 cells treated with LDHs-SRF. For the in vivo experiment, LDHs-SRF were administered to rat models of CCl4-induced liver fibrosis. H&E, masson and sirius red staining showed that LDHs-SRF could significantly reduce inflammatory infiltrate and collagen fiber deposition and immunohistochemical results found that LDHs-SRF treatment significantly inhibited the protein expressions of α-SMA in the liver, these results suggesting that LDHs-SRF exhibited better anti-fibrotic effect than SRF alone and significantly inhibited the proliferation and activation of rat hepatic stellate cells and collagen fiber synthesis.
研究领域:
药理学
·
细胞生物学
·
肝病学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jin Cui,Gongzheng Wang,Li Xian Yip,Mengzhen Dong,Mengyao Mu,Liya Tian,Yuan Gao,Qing Fan,Qiang Zhu,Xinya Zhao,Xueli Xu,David Tai Leong,Xiao Sun
Early detection and timely intervention are essential to prevent liver fibrosis from progressing to cirrhosis or hepatocellular carcinoma. Herein, utilizing the enhanced ferritin-manganese interaction by nanoplatinum growth, a novel ferritin-platinum-manganese magnetic resonance nanoplatform with RGD grafting and metformin loading (FNMMR) is developed. RGD can enhance the targeting ability of the nanoplatform toward integrin αVβ3 on activated hepatic stellate cells (aHSCs) in liver fibrosis. Systemic delivery of FNMMR shows clear degree-dependent magnetic resonance contrast enhancement in liver fibrosis. 3D reconstruction techniques and histogram-based features are achieved to qualitatively and quantitatively analyze the inhomogeneous liver fibrosis areas. FNMMR with catalase-like activity can catalyze the generation of O 2 to alleviate the liver fibrosis hypoxia and inhibit the expression of HIF-1α, blocking the TGF-β1/Smad signaling pathway. In addition, metformin shows synergy with HIF-1α reduction in blocking the TGF-β1/Smad pathway, effectively inhibiting the activation of HSCs and reducing collagen formation. Furthermore, FNMMR can achieve real-time anti-fibrotic therapy monitoring by magnetic resonance imaging. Importantly, no obvious side effects can be observed in both histological and hematology examinations. Therefore, this work presents a novel nanoplatform for accurate liver fibrosis diagnosis and synergistic anti-fibrotic therapy with real-time monitoring.
研究领域:
医学影像
·
纳米技术
·
药理学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）